# Tumor-associated pDC (TApDC) and HIV infection in programing tumor microenvironment

> **NIH NIH P30** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $249,999

## Abstract

Project summary
People with HIV (PWH) are living longer and healthier lives thanks to combination antiretroviral therapy (cART).
However, they are experiencing an increased risk for non-AIDS–defining cancers. About 10% of deaths in PWH
in the U.S. are now due to non–AIDS-defining cancers, including hepatocellular carcinoma (HCC) and Non-small
Cell Lung Cancer (NSCLC). Immunotherapy using Immune Checkpoint Inhibitors (ICIs) has improved outcomes
of HCC and NSCLC in the general population, but outcomes in PWH are less clear. The tumor immune
microenvironment (TIME) in HCC and NSCLC is characterized by high levels of tumor-associated plasmacytoid
dendritic cells (TApDCs), which contribute to immunosuppression and promote tumor growth. In PWH, even in
those treated with cART, circulating pDCs induce the killing of T cells, reducing their infiltration into tumors and
immunotherapeutic potential. Our long-term goals are to study functions of TApDCs in TIME of HIV-associated
HCC and NSCLC, and to develop novel therapeutics to treat such cancers in PWH. This project is based on our
extensive experience and preliminary results, including the following. i) pDC depletion in HIV-infected humanized
mice rescued anti-HIV CD8+ T cells to control HIV persistence. ii) pDC depletion resolved inflammation, reversed
immune exhaustion and rescued activity of anti-tumor CD8+ T cells. iii) In humanized NSG mice with human
immune cells and liver tumor (HCC-HIT mice), TApDC enhanced human tumor growth, associated with
accumulation of TA-Treg and exhausted CD8 T cells. iv) Depletion of human TApDC in HCC-HIT mice reduced
HCC growth, rescued stem-like CD8 T cells in number and functions, and decreased TA-Tregs. We hypothesize
that the effects of TApDC in TIME are exacerbated by HIV (even during cART) and contribute to more severe
immune suppression or resistance to PD1 ICI immunotherapy. Depletion of TApDC will reprogram TIME to
reduce TA-Treg and rescue anti-tumor T cells that respond to PD-1 ICI therapy. We have established two
humanized mouse models that support HIV infection and human liver cancer (HCC-HIT mice, Drs. Geng and
Su) or human lung cancer (NSCLC-HIT mice, Dr. Heredia). We propose to 1) study how HIV infection affects
tumor growth and TApDC/TIME in HCC and NSCLC and 2) to investigate how TApDC interact with ICIs to control
tumors in HCC-/NSCLC-HIT mice. We will achieve the following milestones in the two years: (i) characterization
of HCC/NSCLC TIME including HIV-enhanced TApDC to suppress T cells and exacerbate tumor growth; and (ii)
preclinical testing of TApDC depletion alone and in combination with PD1 ICI in HCC (HCC-HIT mice) and
NSCLC (NSCLC-HIT mice) with HIV infection. This will set the foundation to establish a strong program in
studying HIV-associated cancers in the UMGCCC. Findings from the project will have a great impact on our
understanding of TApDC in HCC/NSCLC TIME, HIV-induced mechanisms of cancer promotion, and on
discovering a novel thera...

## Key facts

- **NIH application ID:** 11064999
- **Project number:** 3P30CA134274-17S2
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Taofeek K Owonikoko
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,999
- **Award type:** 3
- **Project period:** 2008-08-08 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11064999

## Citation

> US National Institutes of Health, RePORTER application 11064999, Tumor-associated pDC (TApDC) and HIV infection in programing tumor microenvironment (3P30CA134274-17S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11064999. Licensed CC0.

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